Methamphetamine Compromises the Adaptive B Cell-Mediated Immunity to Antigenic Challenge in C57BL/6 Mice

Mitha, Anum N; Chow, Daniela; Vaval, Valerie; Guerrero, P. A.; Rivera-Rodriguez, Dormarie E.; Martinez, Luis R.

doi:10.3389/ftox.2021.629451

Cited by 5 publications

(8 citation statements)

References 41 publications

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“…B cells are important for adaptive immunity especially for humoral or antibody‐based responses and antigen presentation. METH alters B cell tissue infiltration and antibody production suggesting a possible detrimental impact on humoral immunity to infection or autoimmunity 36–38 . Thus, we evaluated whether METH compromises B cell and B memory cell populations as well as their DAT expression (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

“…As shown in Figures 2 and 3, METH did not alter the total number of T and B cells in blood but reduced DAT expression in these immune cells, which is in contrast with studies showing that METH is detrimental to lymphocytes. 5,32,37,51 This could be due to the different model and duration of METH exposure. 52 It is conceivable that METH down-regulates the expression of DAT on the surface of immune cells, thus, compromising the inflammatory or adaptive immune responses.…”

Section: Discussionmentioning

confidence: 99%

“…METH alters B cell tissue infiltration and antibody production suggesting a possible detrimental impact on humoral immunity to infection or autoimmunity. [36][37][38] Thus, we evaluated whether METH compromises B cell and B memory cell populations as well as their DAT expression (Figure 3). We first gated for CD45+ cells (Figure 3A), followed by CD19+ cells (naïve B cells) and CD19+/CD27+ (memory B cells) (Figure 3B).…”

Section: Meth Reduces B Cell Dat Expression That May Impact Humoral R...mentioning

confidence: 99%

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Methamphetamine induces a low dopamine transporter expressing state without altering the total number of peripheral immune cells

Gopinath

Riaz

Miller

et al. 2023

Basic Clin Pharma Tox

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Methamphetamine is a widely abused psychostimulant and one of the main targets of dopamine transporter (DAT). Methamphetamine reduces DAT‐mediated dopamine uptake and stimulates dopamine efflux leading to increased synaptic dopamine levels many folds above baseline. Methamphetamine also targets DAT‐expressing peripheral immune cells, reduces wound healing and increases infection susceptibility. Peripheral immune cells such as myeloid cells, B cells and T cells express DAT. DAT activity on monocytes and macrophages exhibits immune suppressive properties via an autocrine paracrine mechanism, where deletion or inhibition of DAT activity increases inflammatory responses. In this study, utilizing a mouse model of daily single dose of methamphetamine administration, we investigated the impact of the drug on DAT expression in peripheral immune cells. We found in methamphetamine‐treated mice that DAT expression was down‐regulated in most of the innate and adaptive immune cells. Methamphetamine did not increase or decrease the total number of innate and adaptive immune cells but changed their immunophenotype to low‐DAT‐expressing phenotype. Moreover, serum cytokine distributions were altered in methamphetamine‐treated mice. Therefore, resembling its effect in the CNS, in the periphery, methamphetamine regulates DAT expression on peripheral immune cell subsets, potentially describing methamphetamine regulation of peripheral immunity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Meth Reduces B Cell Dat Expression That May Impact Humoral R...mentioning

confidence: 99%

See 1 more Smart Citation

Methamphetamine induces a low dopamine transporter expressing state without altering the total number of peripheral immune cells

Gopinath

Riaz

Miller

et al. 2023

Basic Clin Pharma Tox

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“…The drug also reduces the production of IL-4 and IFN-γ in splenocytes isolated from METH-treated animals and exposed to ovalbumin ex vivo (Wey et al, 2008). The activation of B lymphocytes, which involves T cell-dependent and T cell-independent antigen, was recently explored in C57BL/6 mice to determine the effects of METH on antibody-mediated immunity to ovalbumin (T cell-dependent) and LPS (T cellindependent) (Mitha et al, 2021). Pulmonary and splenic tissue infiltration by B cells was enhanced by METH seven days post-antigenic challenge.…”

Section: B Cellsmentioning

confidence: 99%

Methamphetamine Dysregulation of the Central Nervous System and Peripheral Immunity

Miller

Gopinath

et al. 2021

J Pharmacol Exp Ther

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Methamphetamine (METH) is a potent psychostimulant that increases extracellular monoamines such as dopamine and norepinephrine and affects multiple tissue and cell types in the CNS and peripheral immune cells. The reinforcing properties of METH underlie its significant abuse potential and dysregulation of peripheral immunity and central nervous system functions. Together, the constellation of METH's effects on cellular targets and regulatory processes has led to immune suppression and neurodegeneration in METH addicts and animal models of METH exposure. Here we extensively review many of the cell types and mechanisms of METH-induced dysregulation of the central nervous and peripheral immune systems. Significance StatementEmerging research has begun to show that methamphetamine regulates dopaminergic neuronal activity. In addition, METH affects non-neuronal brain cells, such as microglia and astrocytes, and immunological cells of the periphery. Concurrent disruption of bidirectional communication between dopaminergic neurons and glia in the CNS and peripheral immune cell dysregulation gives rise to a constellation of dysfunctional neuronal, cell, and tissue types. Therefore, understanding the pathophysiology of METH requires consideration of the multiple targets at the interface between basic and clinical neuroscience.

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“…In addition, the immunosuppressive effects of METH were shown in animal models, including decreased NK activity and proliferation rate in splenic lymphocytes (Yu et al, 2002 ; Akiyama et al, 2008 ). It has also been reported that METH administration could promote B cell infiltration in the spleen and lung in mice (Mitha et al, 2021 ). However, we observed no significant change in the number of NK and B cells in patients undergoing METH withdrawal.…”

Section: Discussionmentioning

confidence: 90%

Dynamic immune and exosome transcriptomic responses in patients undergoing psychostimulant methamphetamine withdrawal

Zhang²,

Ma³

et al. 2022

Front. Cell. Neurosci.

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Methamphetamine (METH) addiction and withdrawal cause serious harm to both the immune system and nervous system. However, the pathogenesis remains largely unknown. Herein, we investigated the peripheral cytokines and exosomal transcriptome regulatory networks in the patients with METH use disorders (MUDs) undergoing withdrawal. Twenty-seven cytokines were simultaneously assessed in 51 subjects, including 22 at the acute withdrawal (AW) stage and 29 at the protracted withdrawal (PW) stage, and 31 age and gender-matched healthy controls (HCs). Compared to the HCs, significantly decreased levels of interleukin (IL)-1β, IL-9, IL-15, Basic FGF, and MIP1a, increased levels of IL-1rα, IL-6, Eotaxin IP-10, VEGF, and RANTES were identified in AW. These disturbances were mostly or partly restored to the baseline in PW. However, the cytokines IL-6, IL-7, and IL-12p70 were consistently increased even after one year of withdrawal. Besides, a significant decrease in CD3+T and CD4+T cell numbers was observed in AW, and the diminishment was restored to baseline in PW. Comparatively, there were no statistically significant changes in CD8+T, NK, and B cells. Furthermore, the exosomal mRNAs and long non-coding RNAs (lncRNA) were profiled, and the lncRNA-miRNA-mRNA networks were constructed and associated with METH AW and PW stages. Notably, the chemokine signaling was remarkably upregulated during AW. By contrast, the differentially expressed mRNAs/lincRNAs were significantly enriched in neurodegeneration-related diseases. Taken together, a group of METH withdrawal-related cytokines and exosomal mRNA/lncRNA regulatory networks were obtained, which provides a useful experimental and theoretical basis for further understanding of the pathogenesis of the withdrawal symptoms in MUDs.

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Methamphetamine Compromises the Adaptive B Cell-Mediated Immunity to Antigenic Challenge in C57BL/6 Mice

Cited by 5 publications

References 41 publications

Methamphetamine induces a low dopamine transporter expressing state without altering the total number of peripheral immune cells

Methamphetamine induces a low dopamine transporter expressing state without altering the total number of peripheral immune cells

Methamphetamine Dysregulation of the Central Nervous System and Peripheral Immunity

Dynamic immune and exosome transcriptomic responses in patients undergoing psychostimulant methamphetamine withdrawal

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